Carcinogenesis Advance Access published online on January 23, 2004
Carcinogenesis, doi:10.1093/carcin/bgh091
© 2004 by Oxford University Press
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CARCINOGENESIS
1 Inserm UMR-S 392, Université Louis Pasteur de Strasbourg, F-67400 Illkirch, France
* Corresponding author. E-mail: scholler{at}pharma.u-strasbg.fr.
Received 25 September 2003
; revised 22 December 2003
; accepted 14 January 2004
Several studies reported linkage between bacterial infections and carcinogenesis. S. bovis, was traditionally considered as a lower grade pathogen frequently involved in bacteremia and endocarditis. This bacteria became important in human health since it was shown that 25% to 80% of patients who presented a S. bovis bacteremia had also a colorectal tumour. Moreover, in previous experiments, we demonstrated that S. bovis or S. bovis wall extracted antigens (WEA) were able to promote carcinogenesis in rats. The aim of the present study was (i) to identify the S. bovis proteins responsible for in vitro proinflammatory properties, (ii) to purify them, (iii) to examine their ability to stimulate in vitro IL-8 and COX-2 expression by human colon cancer cells and (iv) to assess in vivo their pro-carcinogenic potential in a rat model of colon carcinogenesis. The purified S300 fraction, as determined by proteomic analysis, contained 72 protein spots in 2D gel electrophoresis representing 12 different proteins able to trigger human epithelial colonic Caco-2 cells and rat colonic mucosa to release CXC chemokines (human IL-8 or rat CINC/GRO) and PGE2, correlated with an in vitro overexpression of COX-2. Moreover, these proteins were highly effective in the promotion of pre-neoplastic lesions in azoxymethane-treated rats. In the presence of these proteins, Caco-2 cells exhibited enhanced phosphorylation of the 3 classes of MAP Kinases. Our results show a relationship between the pro-inflammatory potential of S. bovis proteins and their pro-carcinogenic properties, confirming the linkage between inflammation and colon carcinogenesis. These data support the hypothesis that colonic bacteria can contribute to cancer development particularly in chronic infection/inflammation diseases where bacterial components may interfere with cell function.
Carcinogenic properties of proteins with pro-inflammatory activity from Streptococcus bovis
2 CNRS UMR 7509, CNRS-Université Louis Pasteur, F-67087 Strasbourg, Cedex 2, France
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